Engineering biosafe cisplatin loaded nanostructured lipid carrier: optimisation, synthesis, pharmacokinetics and biodistribution.

Low aqueous solubility, adverse effects of Cisplatin includes hepatotoxicity and nephrotoxicity necessitates development of nanoparticulate drug delivery. The study pertains to development of CisNLC (Cisplatin loaded Nanostructured Lipid Carrier) by ultrasonication. Physical characterisation includes particle size, zeta potential, TEM, SEM-EDX, DSC. Its ex vivo biocompatibility, pharmacokinetics and biodistribution along with acute toxicity induced oxidative stress in Balb/c mice were evaluated. The mean particle diameter of CisNLC was observed to be 141.5 ± 3.86 nm with zeta potential of -41.5 ± 1.62 mV. In vitro release studies at pH 7.4 and 5.8 showed burst release following a sustained release pattern post-72 h. CisNLC showed anticancer efficacy against PA-1. Negligible ex vivo haemolysis indicated bio-compatibility. Improved pharmacokinetics of CisNLC was observed. Acute toxicity and oxidative stress evaluation proved negligible toxicity by CisNLC. The formulated CisNLC had a good physical stability, biocompatible, indicated enhanced circulation and caused negligible toxicity on liver and kidney as compared to pure Cis.

Role of Imaging in Childhood Arthritis.

ABSTRACT: Imaging plays a pivotal role in the management of various childhood arthritis. Conventional radiography is the most commonly ordered imaging modality for the evaluation of arthritis. Owing to their higher sensitivity for detecting synovitis, magnetic resonance imaging and ultrasonography are increasingly being used to guide clinical management of various forms of arthritis, especially juvenile idiopathic arthritis. Magnetic resonance imaging is a preferred modality for evaluating more complex sites such as the sacroiliac joint. In this review, we have discussed the rational use and the characteristic imaging features of common childhood arthritis.

Endotracheal Tube Placement Confirmation with Bedside Ultrasonography in the Pediatric Intensive Care Unit: A Validation Study.

Critically ill patients who are intubated undergo multiple chest X-rays (CXRs) to determine endotracheal tube position; however, other modalities can save time, medical expenses, and radiation exposure. In this article, we evaluated the validity and interrater reliability of ultrasound to confirm endotracheal tube (ETT) position in patients. A prospective study was performed on intubated patients with cuffed ETTs. The accuracy of ultrasound to confirm correct ETT placement in 92 patients was 97.8%. Sensitivity, positive predictive value, and agreement of 97.7, 93.3, and 91.3% were found on comparing ultrasound to CXR findings. Ultrasound is feasible, reliable, and has good interrater reliability in assessing correct ETT position in children.

Redox resetting of cisplatin-resistant ovarian cancer cells by cisplatin-encapsulated nanostructured lipid carriers.

Aim: To sensitize cisplatin (Cis)-resistant ovarian cancer cells toward Cis using Cis-loaded nanostructured lipid carriers (CisNLCs). Materials & methods: CisNLCs were synthesized and characterized using dynamic light scattering, Fourier transform IR and x-ray diffraction (XRD). Sensitivity of PA-1 and CaOV3 cells to Cis and its biotoxicity were assessed. Further, expression of the Cis-resistance markers GSTPi and ATP7B, and apoptotic markers Bax, Bcl2 and Cas9 were quantified by real-time PCR. Results: The size of synthesized CisNLCs was approximately 179.3 ± 2.32 nm and surface charge was -33.9 ± 1.47 mV. IC50 was 210 µg/ml in PA-1 and 500 µg/ml in CaOV3. CisNLCs modulated reactive oxygen species levels in CaOV3 cells. Reduced GSTPi and decreased Cis efflux via ATP7B sequestration caused Cis to accumulate in cytoplasm, thereby augmenting apoptosis in cells. Conclusion: CisNLCs sensitize CaOV3 by redox resetting, indicating their immense therapeutic potential.

Hyaluronate-functionalized hydroxyapatite nanoparticles laden with methotrexate and teriflunomide for the treatment of rheumatoid arthritis.

Rheumatoid arthritis (RA), an autoimmune inflammatory disorder is currently incurable. Methotrexate and Teriflunomide are routinely prescribed drugs but their uses are limited due to severe hepatotoxicity. Hyaluronic acid (HYA) is a targeting ligand for CD44 receptors overexpressed on inflamed macrophages. The present investigation aimed at design and fabrication of HYA coated hydroxyapatite nanoparticles (HA-NPs) loaded with Methotrexate (MTX) and Teriflunomide (TEF) (HAMT-NPs) to form HYA-HAMT-NPs for the treatment of RA. HYA-HAMT-NPs showed the nanoscale size of 274.9 ± 64 nm along with a zeta potential value of -26.80 ± 6.08 mV. FTIR spectra of HYA and HYA-HAMT-NPs proved the coating of HYA on HYA-HAMT-NPs. HYA-HAMT-NPs showed less cell viability compared to drugs on RAW 264.7 macrophage cells. A biodistribution study by gamma scintigraphy imaging further strengthened the results by revealing significantly higher (p<0.05) percentage radioactivity (76.76%) of HYA-HAMT-NPs in the synovial region. The results obtained by pharmacodynamic studies ensured the better efficacy of HYA-HAMT-NPs in preventing disease progression and promoting articular regeneration. Under hepatotoxicity evaluation, liver histopathology and liver enzyme assay revealed ~29% hepatotoxicity was reduced by HYA-HAMT-NPs when compared to conventional FOLITRAX-10 and AUBAGIO oral treatments. Overall, the results suggest that HYA-HAMT-NP is a promising delivery system to avoid drug-induced hepatotoxicity in RA.

Assessing the potential of lignin nanoparticles as drug carrier: Synthesis, cytotoxicity and genotoxicity studies.

Lignin nanoparticles synthesis is among recent developments in lignin valorization especially for biomedical applications. In this study, a new technique where complete self-assembling of lignin was ensured by simultaneous solvent displacement and flash pH change was used to optimize particle size of blank lignin nanoparticles (BLNPs) for suitability in cell uptake along with maximized yield. To establish BLNPs as drug carrier, safety studies including hemocompatibility, cytotoxicity and elaborate genotoxicity studies on Drosophila melanogaster as a model organism were done. Finally, irinotecan loaded lignin nanoparticles (DLNPs) were synthesized to establish their drug carrying potential and thorough in vitro characterization was performed. BLNPs with controllable size (⁓152 nm), low polydispersity (<0.2), maximized yield (>65%), negative surface charge (-22 to -23 mV), spherical shape and smooth surface were obtained with acceptable %hemolysis (<2%). In vitro cytotoxicity studies revealed that BLNPs were significantly toxic (74.38 ± 4.74%) in human breast adenocarcinoma (MCF-7), slightly toxic (38.8 ± 4.70%) in human alveolar epithelial adenocarcinoma (A-549) and insignificantly toxic (15.89 ± 2.84%) to human embryonic kidney (HEK-293) cells. BLNPs showed concentration dependent early neuronal defects in Drosophila, but nuclei fragmentation and gut cell damage were absent. Sustained release DLNPs with high drug loading reduced the IC50 value of irinotecan by almost 3 folds.

Copper-Gallic Acid Nanoscale Metal-Organic Framework for Combined Drug Delivery and Photodynamic Therapy.

In this paper, we report the synthesis of bioactive copper-gallic acid nanoscale metal-organic framework for the codelivery of anticancer agent (gallic acid) and photosensitizer (methylene blue) to cancer cells. A supramolecular coordination complex of copper-bioactive frameworks (bio MOFs) were employed as the carrier of two anticancer agents. The first one is the natural phenolic acid (gallic acid), which forms a part of the framework structure (building block). The other one is the photosensitizer methylene blue, loaded as a guest molecule within the amphiphilic pores of the framework. In vitro cytotoxicity and in vivo tumor regression assays revealed enhanced cytotoxicity of dual drug nanoframework when compared with the equivalent dosages of free drugs in the presence of light.

Utility of ureteric jet: A simple yet useful tool for the evaluation of complex urogenital anomaly.

In infants and young children with suspicion of genitourinary tract anomalies, ultrasonography (USG) is usually the first imaging modality. Advantages of USG are well described. In the evaluation of complex congenital urogenital anomalies, ultrasound examination needs to be tailored according to the clinical suspicion and to yield maximum information. Primary megaureter is a congenital anomaly, which is associated with dilatation of ureter above an adynamic segment at the vesicoureteric junction (VUJ). Two different types are described in the literature: refluxing and obstructive. Absence of ureteric jet on USG in conjunction with vesicoureteric reflux (VUR) on voiding cystourethrogram (VCUG) prompts to the diagnosis of refluxing type of obstructed megaureter. Here we describe a case of duplex moiety with refluxing type of obstructed megaureter, where gray-scale USG and real-time color Doppler evaluation of the ureteric jet established the diagnosis. The aperistaltic segment of lower ureter near the VUJ with an absence of ureteric jet for the same moiety suggested the possibility of an obstructed megaureter. VUR was demonstrated on VCUG; thus, pointing toward a diagnosis of obstructed refluxing megaureter.

Placental mesenchymal dysplasia: What every radiologist needs to know.

Placental mesenchymal dysplasia (PMD) is an uncommon vascular anomaly of the placenta characterized by placentomegaly with multicystic placental lesion on ultrasonography and mesenchymal stem villous hyperplasia on histopathology. Placental mesenchymal dysplasia should be considered in the differential diagnosis of cases of multicystic placental lesion such as molar pregnancy, chorioangioma, subchorionic hematoma, and spontaneous abortion with hydropic placental changes. However, lack of high-velocity signals inside the lesion and a normal karyotype favor a diagnosis of PMD. PMD must be differentiated from gestational trophoblastic disease because management and outcomes differ. We report the case of an 18-year-old female at 15 weeks of gestation with sonographic findings suggestive of placental mesenchymal dysplasia. The diagnosis was confirmed on histopathology.

Urologic manifestations of inflammatory pseudotumor: Report of 2 cases and review of the literature.

We report two adult patients with varied urologic symptoms who were found to have inflammatory pseudotumor on histopathology. The first patient had a large, solid, enhancing retroperitoneal mass lesion and presented with increased frequency of urination and recurrent urinary tract infections. The second patient had an obstructing left distal ureteric stricture and presented with painless hematuria. Though preoperative radiological diagnosis of this entity is not feasible, the present article illustrates the imaging findings in this unusual disease entity with review of the relevant literature.